Insight on the Promising 52-Week KarXT Data with Rishi Kakar, MD


In an interview with HCPLive, Rishi Kakar, MD, discussed the positive long-term xanomeline-trospium data from EMERGENT-4.

Once again, data on KarXT (xanomeline-trospium) for schizophrenia shows promise.

Bristol Myers Squibb announced on April 6, 2024, the optimistic results of EMERGENT-4, a phase 3 open-label extension trial evaluating the long-term efficacy of xanomeline-trospium in adults with schizophrenia.1 The data demonstrates xanomeline tropism brings meaningful reductions in the symptoms of schizophrenia at 52 weeks.

“The drug was not something that stopped its effect midway through, which I think is very promising because you want to see [that] the effect of these medications is maintaining,” said lead investigator Rishi Kakar, MD, of Segal Trials, in a recent interview with HCPLive.

As a muscarinic drug, xanomeline-trospium stands apart from all other schizophrenia treatments out there.2 Rather than regulating the dopamine receptor, xanomeline-trospium indirectly modules the dopamine and neurotransmitters responsible for schizophrenia symptoms.

Xanomeline-trospium was evaluated in the EMERGENT program, made up of 5 trials. The first 3 trials compared xanomeline-trospium with a placebo to evaluate efficacy and safety, and 2 trials assessed the drug’s long-term safety. Back on November 29, 2023, the US Food and Drug Administrated accepted the New Drug Application (NDA) for xanomeline-trospium for the treatment of adults with schizophrenia.3

In the interview, Kakar discussed the significance of the 52-week long-term data.

“Over 75% of the participants had at least a 30% improvement in the symptoms at the length of 52 weeks,” he said. “So, I think that's a very promising data.”

The trial had positive results regarding safety. Many patients on schizophrenia medications worry about metabolic symptoms, such as weight gain, diabetes, increased glucose, and adverse events.

“The patient and the caregiver often have to decide is it worth it is a tradeoff really worth it for me to have a drug that's maybe effective, but also has these side effects long term,” Kakar said. “I think that's where the EMERGENT program is now. [It]s] really promising because the data looked at not just the effectiveness over 52 weeks, but also looked at the side effect profile the tolerability over the 52-week period.”

Unlike other schizophrenia medications which are linked to significant weight gain, data revealed xanomeline-trospium over 52 weeks made people lose weight—about 2.6 kilograms over 32 weeks.

“Clinicians often have to decide a subtle balance between the effectiveness of a particular medication and then its safety profile long term,” Kakar said. “I always say that clinicians have to often decide: Am I doing more good than harm long-term as I prescribe these medications to our patients? So, I think KarXT, because of [its] unique mechanism of action, fits into that sort of treatment regimen.”


  1. Derman, C. KarXT Effective in Improving Schizophrenia Symptoms at 52 Weeks. HCPLive. April 8, 2024. Accessed April 16, 2024.
  2. Derman, C. Rishi Kakar, MD: EMERGENT Trials, FDA Accepts Xanomeline-Trospium Application. December 1, 2023. Accessed April 16, 2024.
  3. Derman, C. FDA Accepts Xanomeline-Trospium Drug Application for Schizophrenia Treatment. HCPLive. November 29, 2023. Accessed April 16, 2024.
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